The biological function of nucleic acids, such as RNA, is mediated by their structures. For example, mRNA is generally thought of as a linear molecule which contains the information for directing protein synthesis within the sequence of ribonucleotides. Studies have revealed a number of secondary and tertiary structures in mRNA which are important for its function (Tinoco et al. (1987) Symp. Quant. Biol. 52:135). Secondary structural elements in RNA are formed largely by Watson-Crick type interactions between different regions of the same RNA molecule. Important secondary structural elements include intramolecular double stranded regions, hairpin loops, bulges in duplex RNA and internal loops. Tertiary structural elements are formed when secondary structural elements come in contact with each other or with single stranded regions to produce a more complex three dimensional structure.
Very little is known about the precise three dimensional structures of nucleic acids, including in particular RNA. However, there have been a number of research efforts which have shown that RNA structures, including single stranded, secondary and tertiary structures, have important biological functions beyond simply encoding the information to make proteins in linear sequences (Resnekov et al. (1989) J. Biol. Chem. 264:9953; Tinoco et al. (1987) Symp. Quant. Biol. 52:135; Tuerk et al. (1988) PNAS USA 85:1364; and Larson et al. (1987) Mol. Cell. Biochem. 74:5). Thus, the development of approaches for the evaluation of the structure of nucleic acid molecules, such as RNA, represents a current and ongoing need in the art.